High-pressure applications in medicine and pharmacology

Abstract

High pressure has emerged as an important tool to tackle several problems in medicine andbiotechnology. Misfolded proteins, aggregates and amyloids have been studied, which pointtoward the understanding of the protein misfolding diseases. High hydrostatic pressure(HHP) has also been used to dissociate non-amyloid aggregates and inclusion bodies. Thediverse range of diseases that result from protein misfolding has made this theme animportant research focus for pharmaceutical and biotech companies. The use of highpressure promises to contribute to identifying the mechanisms behind these defects andcreating therapies against these diseases. High pressure has also been used to study virusesand other infectious agents for the purpose of sterilization and in the development ofvaccines. Using pressure, we have detected the presence of a ribonucleoproteinintermediate, where the coat protein is partially unfolded but bound to RNA.These intermediates are potential targets for antiviral compounds. The ability ofpressure to inactivate viruses, prions and bacteria has been evaluated with a viewtoward the applications of vaccine development and virus sterilization. Recentstudies demonstrate that pressure causes virus inactivation while preserving theimmunogenic properties. There is increasing evidence that a high-pressure cycle traps avirus in the ‘fusion intermediate state’, not infectious but highly immunogenic.